Little progress has been made in the direct characterization of gastrointestinal peptide hormone-receptor interactions. These types of studies generally rely on radiolabeled hormones of high specific activity. There are serious experimental difficulties, however, in the direct radioiodination of gastrointestinal peptide hormones with retention of biologic properties. Many of these problems could be avoided by attaching a prosthetic group prelabeled with 125I to the peptide. A new reagent, methyl p-hydroxybenzimidate (MPHBIM) can be prepared to specific activities of 2000 Ci/mmole using carrier-free Na125I and coupled by amidine linkage to peptides through alpha-and epsilon-amino groups. This iodinated imidoester (IIE) of MPHBIM will be coupled to the biologically active C-terminal octapeptide of cholecystokinin (OP-CCK) and secretin. After purification, the effect of IIE-modification on the biologic and immunochemical properties of these hormones will be determined. Hormone-receptor interactions in dispersed pancreatic acinar cells will be studied using these high specific activity IIE-derivatives. Specific binding will be demonstrated by the following criteria: reversibility, temperature dependence of association and dissociation, saturability, competitive inhibition of radiolabeled-OP-CCK and -secretin by structurally related derivatives only, and correlation of binding to biologic potency. Finally structure-function studies using the radiolabeled derivatives and various synthetic fragements will enable us to delineate binding and biologic activity regions in these hormones. We hope to establish a direct correlation between these binding studies and previous biochemical data that relate to hormonal control mechanisms in dispersed pancreatic acinar cells.